Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans

Abstract

Background:Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception.Methods:A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness.Results:Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body.Conclusions:Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans.

Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity

“…Thus, administration of vaporized Sal A to human volunteers leads to intense psychotropic effects including hallucinations, disconnection from external reality, and altered interoceptive abilities (31). To date, it is not known if Collys exhibit hallucinogenic effects.…”

Hallucinations, somatic‐functional disorders of PD‐DLB as expressions of thalamic dysfunction

“…DMN decoupling is also described to occur in psychotic states and after the administration of psychedelic drugs . Most psychedelic drugs (eg, lysergic acid diethylamide, mescaline) are active on a subset of serotonin receptors (5‐HT 2A ), and induce production of complex multimodal hallucinations, delirium, and residual psychosis, whereas the K‐opioid agonist, salvinorin, has been described to induce mind‐body dissociation that breaks the borders of the somatic self and induces a dysperceptive state in which bodily sensations are undifferentiated from external stimuli or autobiographic memories . Drugs acting on these receptors represent potential new targets for SFD‐related research.…”

Clinical applications of hallucinogens: A review.

“…Several controlled studies have been published recently describing behavioral, subjective, and physiological effects of SA (Addy, 2012; Addy et al, 2015; Johnson et al, 2011; MacLean et al, 2013; Maqueda et al, 2015, 2016; Mendelson et al, 2011; Pichini et al, 2005; Siebert, 1994). None of these studies reported serious adverse events or sustained negative effects.…”

“…None of these studies reported serious adverse events or sustained negative effects. Inhaled SA leads to acute psychotomimetic effects (Ranganathan et al, 2012), intense perceptual alterations (Addy, 2012; Addy et al, 2015; MacLean et al, 2013; Ranganathan et al, 2012), dissociative effects (MacLean et al, 2013; Maqueda et al, 2015), elevated cortisol and prolactin, and decreased resting state EEG spectral power (Ranganathan et al, 2012). Peak plasma levels of inhaled SA were found to occur 2 minutes after inhalation, and to directly correspond with participant and observer ratings of subjective effects (Johnson et al, 2016).…”